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Aop: 428

Title

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Binding of S-protein to ACE2 in enterocytes induces ACE2 dysregulation leading to gut dysbiosis

Short name

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ACE2 dysregulation leads to gut dysbiosis

Graphical Representation

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Click to download graphical representation template Explore AOP in a Third Party Tool

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Authors

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Laure-Alix Clerbaux, Julija Filipovska, Amalia Munoz-Pineiro, Lucia Grenga

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section. More help

Cataia Ives (email point of contact)

Contributors

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Laure-Alix Clerbaux
Julija Filipovska
Cataia Ives

Status

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Author status	OECD status	OECD project	SAAOP status
Under development: Not open for comment. Do not cite	Under Development	1.96	Included in OECD Work Plan

This AOP was last modified on July 16, 2022 18:37

Revision dates for related pages

Page	Revision Date/Time
Binding to ACE2	May 17, 2022 10:20
Dysregulation, ACE2 expression and activity	December 05, 2021 12:24
Gut microbiota, alteration	January 04, 2022 10:31
Binding to ACE2 leads to ACE2 dysregulation	February 12, 2022 08:14
ACE2 dysregulation leads to Gut dysbiosis	December 02, 2021 07:16

Abstract

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S-protein binding to ACE2 receptor induces dysregulation of ACE2 physiological functions in the intestines such as modulation of the local renin-angiotensin signaling (RAS) system (10.1152/ajpgi.00099.202) or as a chaperone for dietary amino acid (AA) transporters in the intestines, such as the tryptophan transporter B⁰AT1 (Slc6a19) (10.1042/CS20200477; 10.1053/j.gastro.2008.10.055). The gastrointestinal RAS appears to be involved in numerous processes in the gut including AA, fluid and electrolyte absorption and secretion (10.1111/j.1365-2036.2011.04971.x.). Besides, the gut microbiota is influenced by the host intestinal AA metabolism as gut bacteria use dietary AA for protein synthesis (10.1038/s41598-020-74122-9).

AOP Development Strategy

Context

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AOP428 is developed as a part of the CIAO project, "Modelling the Pathogenesis of COVID-19 Using the Adverse Outcome Pathway (AOP)". The overall goal is to organize and understand the vast amount of data that is constantly evolving as a result of the COVID-19 pandemic and identify uncertainties and knowledge gaps that may be missing using the AOP framework. Many AOPs were developed in the CIAO project, each AOP focusing on a specific element of the SARS-COV-2 virus responses in humans.

AOP428 focuses on the intestinal part and alteration of the gut microbiota via ACE2 dysregulation.

Strategy

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Summary of the AOP

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Events:

Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help

Type	Event ID	Title	Short name

MIE

1739

Binding to ACE2

KE	1854	Dysregulation, ACE2 expression and activity	ACE2 dysregulation
KE	1954	Gut microbiota, alteration	Gut dysbiosis

Relationships Between Two Key Events (Including MIEs and AOs)

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Title	Adjacency	Evidence	Quantitative Understanding

Binding to ACE2 leads to ACE2 dysregulation	adjacent	Moderate
ACE2 dysregulation leads to Gut dysbiosis	adjacent	Moderate	Moderate

Network View

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Prototypical Stressors

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Life Stage Applicability

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Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Known Modulating Factors

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

List of the literature that was cited for this AOP. More help